Ariel Tessone

Systemic Delivery of Bone Marrow–Derived Mesenchymal Stem Cells to the Infarcted Myocardium Feasibility, Cell Migration, and Body Distribution

Background—Systemic delivery of bone marrow–derived mesenchymal stem cells (BM-MSCs) is an attractive approach for myocardial repair. We aimed to test this strategy in a rat model after myocardial infarction (MI). Methods and Results—BM-MSCs were obtained from rat bone marrow, expanded in vitro to a purity of >50%, and labeled with 99mTc exametazime, fluorescent dye, LacZ marker gene, or bromodeoxyuridine. Rats were subjected to MI by transient coronary artery occlusion or to sham MI. 99mTc-labeled cells (4×106) were transfused into the left ventricular cavity of MI rats either at 2 or 10 to 14 days after MI and were compared with sham-MI rats or MI rats treated with intravenous infusion. Gamma camera imaging and isolated organ counting 4 hours after intravenous infusion revealed uptake of the 99mTc-labeled cells mainly in the lungs, with significantly smaller amounts in the liver, heart, and spleen. Delivery by left ventricular cavity infusion resulted in drastically lower lung uptake, better uptake in the heart, and specifically higher uptake in infarcted compared with sham-MI hearts. Histological examination at 1 week after infusion identified labeled cells either in the infarcted or border zone but not in remote viable myocardium or sham-MI hearts. Labeled cells were also identified in the lung, liver, spleen, and bone marrow. Conclusions—Systemic intravenous delivery of BM-MSCs to rats after MI, although feasible, is limited by entrapment of the donor cells in the lungs. Direct left ventricular cavity infusion enhances migration and colonization of the cells preferentially to the ischemic myocardium.

Systemic dysregulation of CEACAM1 in melanoma patients.

It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival. Multivariate analysis with neutralization of LDH showed that increased serum CEACAM1 carries a hazard ratio of 2.40. In vitro, soluble CEACAM1 was derived from CEACAM1(+), but neither from CEACAM1(−) melanoma cells nor from CEACAM1(+) lymphocytes, and directly correlated with the number of CEACAM1(+) melanoma cells. Production of soluble CEACAM1 depended on intact de novo protein synthesis and secretion machineries, but not on metalloproteinase function. An unusually high percentage of CEACAM1(+) circulating NK and T lymphocytes was demonstrated in melanoma patients. CEACAM1 inhibited killing activity in functional assays. CEACAM1 expression could not be induced on lymphocytes by serum from patients with high CEACAM1 expression. Further, expression of other NK receptors was impaired, which collectively indicate on a general abnormality. In conclusion, the systemic dysregulation of CEACAM1 in melanoma patients further denotes the role of CEACAM1 in melanoma and may provide a basis for new tumor monitoring and prognostic platforms.

The use of video capture virtual reality in burn rehabilitation: the possibilities.

We independently explored the use of the Sony PlayStation II EyeToy (Sony Corporation, Foster City, CA) as a tool for use in the rehabilitation of patients with severe burns. Intensive occupational and physical therapy is crucial in minimizing and preventing long-term disability for the burn patient; however, the therapist faces a difficult challenge combating the agonizing pain experienced by the patient during therapy. The Sony PlayStation II EyeToy is a projected, video-capture system that, although initially developed as a gaming environment for children, may be a useful application in a rehabilitative context. As compared with other virtual reality systems the EyeToy™ is an efficient rehabilitation tool that is sold commercially at a relatively low cost. This report presents the potential advantages for use of the EyeToy™ as an innovative rehabilitative tool with mitigating effects on pain in burn rehabilitation. This new technology represents a challenging and motivating way for the patient to immerse himself or herself in an alternate reality while undergoing treatment, thereby reducing the pain and discomfort he or she experiences. This simple, affordable technique may prove to heighten the level of patient cooperation and therefore speed the process of rehabilitation and return of functional ability.

Health Related Quality of Life in burn patients – A review of the literature

The burn trauma is multifactorial and involves pathophysiologic processes of all of the bodys systems. The impact it could have on a persons life includes impairments on their esthetic appearance, interpersonal relationships, psychological, social and physical functioning. Previously, the outcomes of burn care were confined in the context of mortality and length of hospital stay. Currently, a shift is afoot from defining good health care as merely the reduction of morbidity and mortality to a more holistic approach that involves aspects of Health Related Quality of Life. In this article we aim to present a concise review of the relevant literature and relevant topics pertaining Health Related Quality of Life and burn.

The Origin of Human Mesenchymal Stromal Cells Dictates Their Reparative Properties

Background Human mesenchymal stromal cells (hMSCs) from adipose cardiac tissue have attracted considerable interest in regard to cell‐based therapies. We aimed to test the hypothesis that hMSCs from the heart and epicardial fat would be better cells for infarct repair. Methods and Results We isolated and grew hMSCs from patients with ischemic heart disease from 4 locations: epicardial fat, pericardial fat, subcutaneous fat, and the right atrium. Significantly, hMSCs from the right atrium and epicardial fat secreted the highest amounts of trophic and inflammatory cytokines, while hMSCs from pericardial and subcutaneous fat secreted the lowest. Relative expression of inflammation‐ and fibrosis‐related genes was considerably higher in hMSCs from the right atrium and epicardial fat than in subcutaneous fat hMSCs. To determine the functional effects of hMSCs, we allocated rats to hMSC transplantation 7 days after myocardial infarction. Atrial hMSCs induced greatest infarct vascularization as well as highest inflammation score 27 days after transplantation. Surprisingly, cardiac dysfunction was worst after transplantation of hMSCs from atrium and epicardial fat and minimal after transplantation of hMSCs from subcutaneous fat. These findings were confirmed by using hMSC transplantation in immunocompromised mice after myocardial infarction. Notably, there was a correlation between tumor necrosis factor‐α secretion from hMSCs and posttransplantation left ventricular remodeling and dysfunction. Conclusions Because of their proinflammatory properties, hMSCs from the right atrium and epicardial fat of cardiac patients could impair heart function after myocardial infarction. Our findings might be relevant to autologous mesenchymal stromal cell therapy and development and progression of ischemic heart disease.

Interventional magnetic resonance imaging for guiding gene and cell transfer in the heart

Background: Interventional magnetic resonance imaging (iMRI) has the potential for guiding interventional cardiac procedures in real time. Objectives: To test the feasibility of iMRI guided gene and cell transfer to the heart and to monitor myocardial remodelling after myocardial infarction in a rat model. Methods: The MRI contrast agent GdDTPA, together with either Evans blue dye, or a recombinant adenovirus encoding the LacZ gene, or primary fibroblasts tagged by BrdU, were injected into the myocardium of rats under iMRI guidance. Rats were killed seven days after the injection and the hearts sectioned to identify the blue dye, LacZ expression, or fibroblast presence, respectively. In a parallel study, left ventricular area was measured before and after myocardial infarction and in sham operated rats by T1 weighted MRI and by echocardiography. Results: Location of GdDTPA enhancement observed with iMRI at the time of injection was correlated with Evans blue stain, β-gal expression, and the primary fibroblast location in histological studies. iMRI and echocardiography measured a comparable increase in left ventricular area at seven and 30 days after myocardial infarction. A good correlation was found between the iMRI and echocardiographic assessment of left ventricular area (r  =  0.70; p < 0.0001) and change in left ventricular area with time (r  =  0.75; p < 0.0001). Conclusions: The results show the feasibility and efficiency of iMRI guided intramyocardial injections, and the ability to monitor heart remodelling using iMRI. Genes, proteins, or cells for tissue engineering could be injected accurately into the myocardial scar under iMRI guidance.

Managing the relationship between quality and cost-effective burn care

In the modern era of fiscal prudence, managing the relationship between quality health care and cost reduction is a complex and challenging task for policy makers and health care providers. Health economics is an applied field that aids in assessing the feasibility of incorporating new interventions in a certain field. Applying these tools when allocating funds for burn care is even more complicated due to the lack of clinical data regarding the cost effectiveness of different aspects in burn care. Herein we review the existing literature and summarize different approaches for achieving cost effective health care in general and in burn care specifically. Special considerations to funds allocation in burn care are also discussed.

Expanded reverse abdominoplasty for reconstruction of burns in the epigastric region and the inframammary fold in female patients.

We report the use of expanded reverse abdominoplasty in three female patients with postburn scars involving the entire epigastric region in which the inframammary folds were effaced, resulting in distortion of breast contour. In two of the patients, tissue expanders were used, and subsequently, reverse abdominoplasty was performed, thus re-creating the inframammary fold. The third patient reported to be pregnant after expanders were placed; therefore, smaller volumes of inflation for tissue expansion were necessary. We believe that this procedure is an optimal solution, both aesthetically and functionally, in respect to other reconstructive techniques in female patients with normal skin inferior to epigastric burns. The surgical technique and results are discussed.

The effect of acellular dermal matrix on drain secretions after immediate prosthetic breast reconstruction

Abstract In recent years the acellular dermal matrix (ADM) has gained popularity in prosthetic breast reconstruction. These procedures involve placement of a closed suction drain in the reconstructed breast. Although it is now widely accepted that ADM has an overall positive effect on the outcome of breast reconstruction, data regarding its effect on postoperative drain secretions is lacking. This study was designed to quantitatively evaluate the influence of ADM on postoperative drain secretions in the setting of immediate prosthetic breast reconstruction (IPBR). This is a prospective, comparative controlled study. Two groups of 16 patients each underwent skin sparing mastectomies (SSM) and IPBR with or without ADM. Closed suction drains were left in all the reconstructed breasts and daily secretion volumes were recorded and compared. Postoperative complications were also noted. Patients in the ADM group showed higher daily and overall secretion volumes compared with patients in the control group (p = 0.014) and the time for removal of the drains was higher by an average of 5 days (13 compared with 8 days, respectively; p = 0.004). There was no correlation between ADM and infection. This study provides the first objective evidence that ADM contributes to elevated and prolonged drain secretions when used for IPBR. This might affect possible prosthesis-related complications (e.g., rotation and malposition, capsular contraction, seroma formation, and infection). This study also noted erythema of the post-mastectomy skin flaps in selected patients, which may be attributable to a local inflammatory reaction to the ADM rather than infection.

Evading a Surgical Pitfall: Mastopexy––Augmentation Made Simple

Many women have a dwindled ptotic breast. The surgical solution for these two concurring problems has two separate procedures: augmentation and mastopexy. Combining these two procedure into one surgery is considered unpredictable and avoided by many physicians. This study presents a revised mastopexy–augmentation technique found to be safer and more simple, enabling these two procedures to be performed together. A retrospective review of 60 patients who underwent surgery by a single surgeon is presented. The presented method has yielded a relatively low reoperation rate of 10% and a high satisfaction rate.